Stent

ABSTRACT

A radially expansible annular stent is disclosed. The stent comprises a plurality of stenting turns around a lumen centred on a longitudinal axis. Adjacent turns of the stent are joined by connector struts. The stent annulus has a wall thickness related to the material from which it is formed. The radial thickness of the connector struts is smaller than that of the stent annulus. A method of making such a stent is also disclosed. The method includes cutting the connector struts from a tubular workpiece with a laser beam. The laser beam is aimed so as to be offset from a longitudinal axis of the workpiece to provide the reduced radial thickness of the connector struts.

PRIORITY

This application is a continuation of U.S. patent application Ser. No.14/045,603, filed Oct. 3, 2013, now U.S. Pat. No. 9,084,691, which is adivision of U.S. patent application Ser. No. 12/514,177, filed May 8,2009, now U.S. Pat. No. 8,551,156, which was filed as a U.S. nationalstage application under 35 USC §371 of International Application No.PCT/EP2007/062155, filed Nov. 9, 2007, which claims priority to U.K.Patent Application No. 0622465.3, filed Nov. 10, 2006, each of which isincorporated by reference in its entirety into this application.

FIELD OF THE INVENTION

This invention relates to a radially-expansible annular stent comprisinga plurality of stenting turns around a lumen centered on a longitudinalaxis, with adjacent turns being joined by connector struts, the stentannulus having a wall thickness that is related to the material of whichit is formed.

BACKGROUND ART

In the field of radially expansible annular stents that are called upon,in use, to resist a radially inwardly directed force from surroundingbodily tissue, in order to maintain a bodily lumen patent, there is acontradictory design requirement. On the one hand, the stent must bestrong enough to keep the lumen patent. On the other hand, the stentprosthesis must be flexible enough to accommodate movement ofsurrounding bodily tissue.

There are two archetypal stent forms. One of them has a stack of closedloop stenting rings, the length direction of the stent being along thelength of the longitudinal axis of the annulus of the stent. The otherarchetype is the helical stent, in which the pattern of struts in thestent matrix performs a spiral path around the longitudinal axis, tocreate an annulus from one end of the stent to the other. Typically,each of the stenting loops is composed of closed periphery repeatingunit cells. See EP-A-481365, FIG. 2. Typically, there are connectorstruts present, periodically through the annular matrix, to set thelongitudinal spacing between adjacent stenting loops. See WO94/17754.

Such a stent is typically made from a seamless straight tubularworkpiece so that its disposition, at rest, and relaxed, is that of atubular cylindrical annulus. Typically, after implantation in the body,it is called upon to conform to an arcuate configuration of the bodilylumen in which it is placed. Such a change of shape necessitates theoccurrence of strain within the matrix. That strain might not behomogeneously distributed throughout the matrix. Important forflexibility of the stent, after placement in the body, is a capacity fortolerating enough strain to give the stent, as such, enough flexibilityto move with the body.

Another aspect of flexibility that is desirable when placing a stent is“radial conformability” by which is meant the ease with which succeedingturns of the stent can take or, after placement in tissue, differentdiameters clearly, when the struts connecting adjacent stenting ringshave enhanced flexibility, an increase of radial conformability is inprospect.

Closed periphery unit cells of the stenting matrix are inherently ratherwell-adapted to provide the required resistance to the radially inwardlypressing force of the bodily tissue. In consequence, it is desirable forany connectors of unit cells, within the matrix, to deliver at least asubstantial portion of the strain needed to allow the stent matrix tomove with the body. Such flexibility in the connector links is notdetrimental to the capability of the stenting loops to push the bodilytissue radially outwardly. For this reason, current stent designs oftenexhibit unit cells with simple straight strut peripheral portions,connected by connector struts that are not short and straight but longand thin. They are often meandering or arcuate or serpentine. There isdiscussed below, with reference to FIG. 1, showing an exemplary stenthaving connector struts of the serpentine kind This extra lengthprovides the connectors with increased capacity to absorb strain anddeliver flexibility to the stent, as such. However, building a stentannulus with convoluted or serpentine connectors adds to the complexityof manufacture and might not assist in meeting other governmentregulatory or quality control requirements.

It is an object of the present invention to ameliorate thesedifficulties.

SUMMARY OF THE INVENTION

According to the present invention, a stent as identified above isimproved by arranging that, for the connector struts, the thickness ofthe struts is smaller than the ambient wall thickness of the stent.

Typically, stents are made from a seamless tubular workpiece of constantwall thickness. The description which follows will provide at least oneway to produce a stent in accordance with the present invention from aseamless tubular workpiece of constant wall thickness.

Nickel-titanium shape memory alloy is a popular material from which tobuild self-expanding transluminally delivered bodily prostheses such asstents. Typically, they are made from the tubular workpiece by computercontrolled laser cutting of slits in the workpiece, thereby to produce amatrix of struts. An attractive way to build stents in accordance withthe present invention is by use of this laser cutting technique, knownper se.

The conventional laser cutting process for making stents is with a laserbeam arranged on a line that extends through the longitudinal axis ofthe stent annulus. However, the state of the art does include proposals,not only from the present applicant in WO 03/075797, WO 2006/010636 andWO 2006/010638 but also from others, such as Langhans et al in US2006/0064153, to orient the laser beam on a line that does not passthrough the longitudinal axis of the annulus. It is this step which isrelied upon, in the presently preferred embodiment and best mode knownto the inventor, as described in detail below. The concept can beconveniently designated “off-axis cutting”.

As will be seen below, an attractive feature of using off-axis lasercutting of the connectors is that one can provide the connectors with atransverse cross-section that is in some way asymmetric in comparisonwith a “conventional” on-axis laser-cut strut. Thus, the connectors inaccordance with the present invention may have a transversecross-section that includes a luminal apex at the intersection of twostraight lines, that apex being the closest approach of the connector tothe longitudinal axis. It can also create a connector having atransverse cross-section that includes an abluminal apex at theintersection of two straight lines, the apex being the point on theconnector furthest away from the longitudinal axis. Such cross-sectionsthrough the connector can reveal a lack of mirror symmetry about a planethat includes the length direction of the connector and the longitudinalaxis of the stent annulus. In other words, we can have a connector inwhich the transverse cross-section reveals a luminal apex and anabluminal apex, and the line passing through both of these apices doesnot also pass through the longitudinal axis of the annulus of the stent.

As will be seen below, an attractive feature of the present invention isthat it enables the creation of stent matrices that combine good radialforce against bodily tissue with good flexibility both in the radiallyexpanded and in the radially compressed dispositions in a design inwhich the connectors are simple, short, substantially straight struts.

The stiffness of a strut of a stent matrix is proportional to the strutwidth but, in relation to the strut thickness, it goes up with the cubeof the thickness. A small reduction of strut thickness can thereforeyield large gains in flexibility. This property is utilised in thepresent invention by providing connector struts with a smaller radialwall thickness than that of the stent annulus.

For a better understanding of the present invention and to show moreclearly how the same may be carried into effect, reference will now bemade, by way of example, to the accompanying drawings. These areincorporated herein and constitute part of this specification. Theyillustrate presently preferred embodiments of the invention and,together with the general description above, and the detaileddescription below, serve to explain the features of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a view from the side of a stent, showing a small portion ofthe strut matrix of the stent that includes one connector strut;

FIGS. 2, 3 and 4 each show diagrammatically a side view of a stentmatrix with four zig-zag stenting rings, wherein FIG. 2 reveals theat-rest, relaxed disposition of the self-expanding stent, FIG. 3 showsthe same stent under pressure from bodily tissue to bend it out of astraight line and FIG. 4 shows the same stent, strained, in response tochanges of radially-inward force on the stent from surrounding bodilytissue, along the length direction of the stent.

FIG. 5 shows schematically in transverse cross-section three differentstent matrix connector strut shapes; and

FIG. 6 is a transverse cross-section like that of FIG. 5, but showing an“asymmetric” connector strut cross-section.

DETAILED DESCRIPTION

Looking first at FIG. 1, the skilled reader will recognise portions oftwo adjacent zig-zag stenting rings 2, 4 and a single connector 6 ofthose two adjacent rings, central in the drawing Figure. That connector6 shows a serpentine form, resembling the letter “S” lying on its sideand with the base of the letter S contiguous with one of the two zig-zagstenting rings 2, 4 and the top of the letter S contiguous with theother of the two stenting rings. Self-evidently, the serpentine form ofthe connector 6 provides the stent matrix with capacity to undergostrain, somewhat additional to the capacity it would have if theserpentine connector 6 were to be replaced by a short straight linkconnecting the two zig-zag stenting rings 2, 4.

Turning to FIG. 2, we see diagrammatically a stent 10 composed of fourzig-zag stenting rings 14, 16, 18 and 20 like the zig-zag rings shown inFIG. 1. The longitudinal straight lines 22 and 24 indicate the generalform of the annulus of the stent. Now looking at FIG. 3, we canrecognize that the annular stent matrix has undergone some strain,especially in the connector struts (not shown) between zig-zag ring 16and zig-zag ring 18 and in the struts next to these connector portions.On the outside of the bend, at position 26, the tensile strain isaccommodated by bending of the struts and, on the inside of the bend, atposition 28, compressive stresses are likewise accommodated by bendingof the struts. Ideally, the stent has sufficient flexibility to continuein the FIG. 3 disposition to deliver radially outwardly resistive force,even while it is bent into the arcuate shape of FIG. 3, away from therelatively more relaxed straight disposition of FIG. 2. One way toachieve good increases in bending flexibility without sacrificing muchradial force delivered by the stent matrix would be to reduce the wallthickness of portions of the stenting ring struts immediately adjacentto the ring connector portions.

FIG. 4 represents a situation in which the lumen in which the stent hasbeen placed exerts a greater radially inward compressive force onzig-zag stenting rings 14 and 16 than on rings 18 and 20. In thissituation, connector struts between zig-zag rings 16 and 18 suffer shearstresses which would bend them into a lazy S-shape such as is apparentfrom FIG. 4. Again, the connector portions of the stent matrix shouldexhibit enough flexibility in the zone between stenting ring 16 and 18to permit the stent to take up a disposition as shown in FIG. 4, atpositions 30 and 32. For this, one needs a significant degree offlexibility in the connectors linking stenting loops 16 and 18.

We turn now to FIGS. 5 and 6 to reveal how such flexibility can beprovided.

Looking first at FIG. 5, a cross-section of a known connector strut T isshown with connector struts R, S of reduced cross-section overlaying it.The connector struts R and S are exemplary embodiments of the presentinvention. The reduced cross-section provides flexibility, as isexplained below.

It is important to grasp that the drawing is schematic. A moment'sthought from the reader will reveal that the trapezium T with sides 50,52, 54 and 56 is not an accurate representation of a sector of atransverse section through an annular workpiece which is the precursorof the stent matrix. Sides 52 and 56 are correctly shown as straightlines, being in a plane that passes through the longitudinal axis of theannular workpiece, straight line 50 ought to be arcuate, being a portionof the luminal wall of the cylindrical lumen defined by the annularworkpiece. Likewise, straight line 54 ought to be an arc of a circlewith a somewhat larger radius than that of the luminal surface of theannular workpiece, to correspond with a portion of the abluminal surfaceof that workpiece.

However, showing sides 50 and 54 as straight lines serves the objectiveof clarity.

Readers will know that, when laser cutting an annular workpiece, withthe beam of the laser on the axis of the annulus, planar flat surfaces,represented by lines 52 and 56, are the usual result.

However, once the possibility is taken up, to orient the laser beam“off-axis” so that the beam direction does not pass through thelongitudinal axis of the annular workpiece and instead passes through alumen of the workpiece, but offset from the longitudinal axis, thenconnector portions or strut cross-sections that are much smaller in areacan readily be produced. FIG. 5 shows two examples, marked R and S, ofsuch connector struts, in cross-section.

The connector strut section R is bounded by four cut-lines of theoff-axis laser, namely, lines 60, 62, 64 and 66. This strutcross-section is truly a diamond rather than a sector of an annulus.Cross-section S is another possibility, with off-axis laser cut-lines70, 72, 74 and 76.

In both cases, these connector strut cross-sections are symmetricalabout a plane that extends through the longitudinal axis of the annulusof the workpiece, and the luminal apex 68 where cut-lines 64 and 66intersect, and the abluminal apex 69 where cut-lines 60 and 62intersect. In section S, the luminal apex is marked 78 and the abluminalapex is marked 80. In both cases, the luminal apex 68, 78 is furtheraway from the longitudinal axis of the annulus than the luminal surfaceof the workpiece, and the abluminal apex 69, 80 is closer to thelongitudinal axis than the abluminal surface of the annular workpiece. Areduction in the radial thickness has a particularly strong contributionto increasing flexibility. The flatter of the two connector strutsmarked S may, therefore, be more advantageous if flexibility is key.

Finally, turning to FIG. 6, we start with the same sector of the sameannular workpiece, referenced with the same numbers, but show within itan asymmetric connector cross-section Q defined by laser cut-lines 90,92, 94 and 96. Just as in FIG. 5, the intersection of cut-lines 94 and96 produces a luminal apex 98 and the intersection of cut-lines 90 and92 is at an abluminal apex 99. However, the plane that extends throughthese two apices 98 and 99, when extended radially inwardly, does notpass through the longitudinal axis of the annular workpiece.

One distinctive aspect of stent technology is how the strut matrixresponds to expansion from a radially compact transluminal deliverydisposition to a radially expanded deployed disposition. Reverting backto FIGS. 1 to 4, zig-zags in the compact disposition are linear strutsseparated by slits, with the slits and struts all lined up with the longaxis of the stent whereas, in the deployed position, the zig-zag ringshave opened out as shown in each of FIGS. 1 to 4. Interesting is howstresses are distributed during the process of expansion from thedelivery to the deployed disposition. The reader will appreciate thatuse of an asymmetric connector form such as shown in FIG. 6 might yielda useful performance enhancement, in bringing peaks and valleys ofzig-zag stenting rings into opposition, as opposed to a less attractive“peak-to-peak” design such as is apparent from FIG. 1. In FIG. 1, peaks(points of inflection) of adjacent zig-zag stenting rings are facingeach other, with the consequence that these peaks are liable to impingeon each other when a deployed stent is forced into an arcuateconfiguration such as is evident from FIG. 3, on the inside of the bend,at position 28. By contrast, use of an asymmetric cross-sectionconnector as shown in FIG. 6, offers the potential to “skew” thestresses undergone by the stent matrix, when expanding into the deployedconfiguration, to such an extent as to displace facing peaks of thezig-zag rings circumferentially with respect to each other, by justenough to carry each peak into a position between two facing peaks ofthe next adjacent zig-zag stenting ring, the better able to accommodatestrain on the inside of a bend such as at position 28 in FIG. 3.

In some applications of stents, a high degree of plaque control iscalled for. Stents for the carotid artery is an example. Control isachieved by use of closed cell matrix structures, with a small mesh sizeand a relatively large number of connectors between adjacent stentingturns. An increasing number of connector struts reduces stentflexibility. The present invention offers a way to mitigate theflexibility problem without reducing the number of connector struts andthus can be particularly helpful in such applications.

The method of manufacture takes an appropriately sized tubularworkpiece. Stenting turns are cut from this workpiece using a laser inthe conventional way. That is, the laser beam follows a predetermineddesign pattern to form stenting struts to produce the stenting turns. Inproducing the stenting struts, the laser beam will be aimed to passthrough the longitudinal axis of the tubular workpiece. The connectorstruts are cut by aiming the laser beam in an offset manner from thelongitudinal axis of the workpiece. The cut is such that the radial wallthickness is reduced as compared to the radial wall thickness of thestenting struts. This may be achieved as in embodiments discussed aboveby creating a luminal or abluminal apex.

Readers of this specification are persons skilled in the art of stentdesign, who will find many other embodiments, once given the concept ofthe present invention in the description above. The description above isexemplary, but not limiting.

Where undulations are embodied in the form of zig-zag struts, thezig-zag struts may include a repeating pattern made of a unit of fourgenerally linear members that extend oblique to the longitudinal axis tointersect each other at three apices spaced apart circumferentially andaxially. Also, the prosthesis can utilize not only the circumferentialbridges but also other bridge configurations in combination.Alternatively, the bridge directly connects a peak of onecircumferential section to another peak of an adjacent circumferentialsection. In yet another alternative, the bridge may connect a peak ofone circumferential section to a trough of an adjacent circumferentialsection. In a further alternative, the bridge can connect a trough ofone circumferential section to a trough of an adjacent circumferentialsection. Moreover, the undulations can be wave-like in pattern. Thewave-like pattern can also be generally sinusoidal in that the patternmay have the general form of a sine wave, whether or not such wave canbe defined by a mathematical function. Alternatively, any wave-likeforms can be employed so long as it has amplitude and displacement. Forexample, a square wave, saw tooth wave, or any applicable wave-likepattern defined by the struts where the struts have substantially equallengths or unequal lengths. And as used herein, the term “implantableprosthesis” is intended to cover not only a bare stent but also coated,covered, encapsulated, bio-resorbable stent or any portion of similarstents.

Bio-active agents can be added to the prosthesis (e.g., either by acoating or via a carrier medium such as resorbable polymers) fordelivery to the host's vessel or duct. The bio-active agents may also beused to coat the entire stent. A material forming the stent or coupledto the stent may include one or more (a) non-genetic therapeutic agents,(b) genetic materials, (c) cells and combinations thereof with (d) otherpolymeric materials.

(a) Non-genetic therapeutic agents include anti-thrombogenic agents suchas heparin, heparin derivatives, urokinase, and PPack(dextrophenylalanine proline arginine chloromethylketone);anti-proliferative agents such as enoxaprin, angiopeptin, or monoclonalantibodies capable of blocking smooth muscle cell proliferation,hirudin, and acetylsalicylic acid; anti-inflammatory agents such asdexamethasone, prednisolone, corticosterone, budesonide, estrogen,sulfasalazine, and mesalamine;antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel,5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones,endostatin, angiostatin and thymidine kinase inhibitors; anestheticagents such as lidocaine, bupivacaine, and ropivacaine; anti-coagulants,an RGD peptide-containing compound, heparin, antithrombin compounds,platelet receptor antagonists, anti-thrombin antibodies, anti-plateletreceptor antibodies, aspirin, prostaglandin inhibitors, plateletinhibitors and tick antiplatelet peptides; vascular cell growthpromoters such as growth factor inhibitors, growth factor receptorantagonists, transcriptional activators, and translational promoters;vascular cell growth inhibitors such as growth factor inhibitors, growthfactor receptor antagonists, transcriptional repressors, translationalrepressors, replication inhibitors, inhibitory antibodies, antibodiesdirected against growth factors, bifunctional molecules consisting of agrowth factor and a cytotoxin, bifunctional molecules consisting of anantibody and a cytotoxin; cholesterol-lowering agents; vasodilatingagents; and agents which interfere with endogenous vascoactivemechanisms.

(b) Genetic materials include anti-sense DNA and RNA, DNA coding for,anti-sense RNA, tRNA or rRNA to replace defective or deficientendogenous molecules, angiogenic factors including growth factors suchas acidic and basic fibroblast growth factors, vascular endothelialgrowth factor epidermal growth factor, transforming growth factor alphaand beta, platelet-derived endothelial growth factor, platelet-derivedgrowth factor, tumor necrosis factor alpha, hepatocyte growth factor andinsulin like growth factor, cell cycle inhibitors including CDinhibitors, thymidine kinase (“TK”) and other agents useful forinterfering with cell proliferation the family of bone morphogenicproteins (“BMPrs”), B1VfiP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7(0P-1), BMP-8, BMP-9, BMP-10, BMP-1, BMP-12, BMP-13, BMP-14, BMP-15, andBMP-16. Desirable BMP's are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 andBMP-7. These dimeric proteins can be provided as homodimers,heterodimers, or combinations thereof, alone or together with othermolecules. Alternatively or, in addition, molecules capable of inducingan upstream or downstream effect of a BMP can be provided. Suchmolecules include any of the “hedgehog” proteins, or the DNA's encodingthem.

(c) Cells can be of human origin (autologous or allogeneic) or from ananimal source (xenogeneic), genetically engineered if desired to deliverproteins of interest at the deployment site. The cells may be providedin a delivery media. The delivery media may be formulated as needed tomaintain cell function and viability.

(d) Suitable polymer materials as a coating or the base material mayinclude polycarboxylic acids, cellulosic polymers, including celluloseacetate and cellulose nitrate, gelatin, polyvinylpyrrolidone,cross-linked polyvinylpyrrolidone, polyanhydrides including maleicanhydride polymers, polyamides, polyvinyl alcohols, copolymers of vinylmonomers such as EVA, polyvinyl ethers, polyvinyl aromatics,polyethylene oxides, glycosaminoglycans, polysaccharides, polyestersincluding polyethylene terephthalate, polyacrylamides, polyethers,polyether sulfone, polycarbonate, polyalkylenes including polypropylene,polyethylene and high molecular weight polyethylene, halogenatedpolyalkylenes including polytetrafluoroethylene, polyurethanes,polyorthoesters, proteins, polypeptides, silicones, siloxane polymers,polylactic acid, polyglycolic acid, polycaprolactone,polyhydroxybutyrate valerate and blends and copolymers thereof, coatingsfrom polymer dispersions such as polyurethane dispersions (for example,BAYHDROL fibrin, collagen and derivatives thereof, polysaccharides suchas celluloses, starches, dextrans, alginates and derivatives, hyaluronicacid, squalene emulsions. Polyacrylic acid, available as HYDROPLUS(Boston Scientific Corporation, Natick, Mass.), and described in U.S.Pat. No. 5,091,205, the disclosure of which is hereby incorporatedherein by reference, is particularly desirable. Even more desirable is acopolymer of polylactic acid and polycaprolactone.

While the invention has been described in terms of particular variationsand illustrative figures, those of ordinary skill in the art willrecognize that the invention is not limited to the variations or figuresdescribed. The method used in the present invention is not limited tothe preferred method discussed above, as will be apparent from theclaims. Further, the improved flexibility of the stents of the presentinvention may be achieved by methods other than the preferred one givenabove, as will be apparent to the skilled person. In addition, wheremethods and steps described above indicate certain events occurring incertain order, those of ordinary skill in the art will recognize thatthe ordering of certain steps may be modified and that suchmodifications are in accordance with the variations of the invention.Additionally, certain of the steps may be performed concurrently in aparallel process when possible, as well as performed sequentially asdescribed above. Therefore, to the extent there are variations of theinvention, which are within the spirit of the disclosure or equivalentto the inventions found in the claims, it is the intent that this patentwill cover those variations as well. Finally, all publications andpatent applications cited in this specification are herein incorporatedby reference in their entirety as if each individual publication orpatent application were specifically and individually put forth herein.

What is claimed is:
 1. A method of making a radially-expansible annularstent having a stent annulus that comprises a plurality of stentingturns around a lumen that is centered on a longitudinal axis, withadjacent turns being joined by connector struts, the stent annulushaving a wall thickness that is related to an annulus material fromwhich it is formed comprising: providing a seamless tubular work piece;cutting the seamless tubular work piece with a laser beam to formconnector struts such that a thickness of the connector struts is cutsmaller than that of the stent annulus and the annulus material fromwhich it is formed, wherein the beam is aimed to not intersect thelongitudinal axis in cutting luminally extending side walls of theconnector struts; cutting the seamless tubular work piece with the beamto form stenting struts interspersed by points of inflection, thestenting turns being formed of the stenting struts, wherein the beam isaimed to intersect the longitudinal axis in cutting luminally extendingside walls of the stenting struts, wherein portions of the stentingturns that are immediately adjacent to the connector struts are formedto have a thickness smaller than that of the stent annulus.
 2. Themethod of claim 1 wherein the connector struts comprise cut surfacesthat intersect at a luminal apex radially further from the longitudinalaxis than a luminal surface of the stent annulus.
 3. The method of claim2 wherein the connector struts comprise cut surfaces that intersect atan abluminal apex that is radially closer to the longitudinal axis thanan abluminal surface of the stent annulus.
 4. The method of claim 3further comprising the step of cutting the cut surfaces intersecting atthe luminal apex and the cut surfaces intersecting at the abluminal apexat different angles, such that a transverse cross-section through theconnector struts reveals a lack of mirror symmetry about a plane thatincludes a length direction of the connector and the longitudinal axisof the stent annulus.
 5. The method of claim 1 wherein the connectorstruts comprise cut surfaces that intersect at an abluminal apex that isradially closer to the longitudinal axis than an abluminal surface ofthe stent annulus.